Biological rhythms are disturbed in the majority of patients with affective disorder. These abnormal rhythms include disruptions of circannual or seasonal rhythms, as observed in seasonal affective disorder, disruptions of circadian or daily rhythms as observed in hyposomnia or hypersomnia, and disruptions of ultradian rhythms such as the disturbed REM cycle that frequently accompanies primary depression. This project focuses on the effects of antidepressant drugs on the mammalian circadian system; we have utilized the Syrian hamster as an animal model. We hypothesize that the mechanism of the antidepressant response to chronic drug therapy includes effects on the mammalian circadian system. Our results support this hypothesis. Previously we reported that clorgyline, a monoamine oxidase inhibitor with antidepressant properties, altered the endogenous expression of the circadian system by a) delaying a large portion of motor activity to the second half of thee activity phase, b) reducing the duration of the rest phase by about 30% and c) decreasing the frequency of the daily biological clock. We also reported that this drug altered the responsiveness of the daily clock to brief environmental light signals. In these past studies, we utilized wheel-running as an index of circadian pacemaker expression. During the past year we have extended our studies to include clorgyline's effects on EEG sleep and telemetred body temperature. During the past year we have extensively explored the effect of clorgyline on the responsiveness of the circadian system to environmental light and dark. These studies indicate that during chronic clorgyline treatment a) the activity-rest cycle becomes progressively more disorganized as the intensity of continuous light is increased b) the capacity of the circadian system to respond normally to dark pulses is altered.